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组织折叠中所涉及的细胞凋亡

在动物发育过程中,上皮组织在一个涉及细胞骨架和细胞连接的细胞自主性重组的过程中折叠成高度有组织的三维结构。

但什么是触发和协调正确折叠所需细胞重塑的信号?

Magali Suzanne及同事以前报告说,凋亡性细胞死亡的一个模式是成年果蝇发育中的腿的关节形成所需的。现在,本文作者利用同一模型系统发现,通过这些凋亡细胞内的一个高度动态化的 “apico-basal myosin II” “缆绳”所产生的一个瞬态拉力充当增加组织张力的一个机械信号。该信号与周围组织中皮层 “myosin II”的稳定化一起来指导相邻细胞的重组和上皮组织折叠。

凋亡细胞在发育中所起的积极作用是一个有趣的发现。


Epithelium folding is a basic morphogenetic event that is essential in transforming simple two-dimensional epithelial sheets into three-dimensional structures in both vertebrates and invertebrates1. Folding has been shown to rely on apical constriction2, 3, 4, 5, 6, 7. The resulting cell-shape changes depend either on adherens junction basal shift2 or on a redistribution of myosin II3,4, 5, 7, which could be driven by mechanical signals8. Yet the initial cellular mechanisms that trigger and coordinate cell remodelling remain largely unknown. Here we unravel the active role of apoptotic cells in initiating morphogenesis, thus revealing a novel mechanism of epithelium folding. We show that, in a live developing tissue, apoptotic cells exert a transient pulling force upon the apical surface of the epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic cells then induce a non-autonomous increase in tissue tension together with cortical myosin II apical stabilization in the surrounding tissue, eventually resulting in epithelium folding. Together our results, supported by a theoretical biophysical three-dimensional model, identify an apoptotic myosin-II-dependent signal as the initial signal leading to cell reorganization and tissue folding. This work further reveals that, far from being passively eliminated as generally assumed (for example, during digit individualization9), apoptotic cells actively influence their surroundings and trigger tissue remodelling through regulation of tissue tension.